More than 100 HPV genotypes are presently distinguished by comparing the DNA sequence of the L1 ORF of each HPV. Two important aspects of the nature of this group of heterogeneous viruses are the way in which specific HPV genotypes are associated with distinct clinical and histological morphologies and the way specific HPV genotypes affect distinct anatomical sites. The former is best evidenced by the HPV type specific cytopathic or cytopathogenic effect (CPE), whereas the latter is suggested by the marked preference of each HPV genotype for specific tissues and sites. Recent studies have also suggested that specific HPV genotypes may target epithelial stem cells at specific anatomical sites. HPV type-specific CPE is the central schema when we analyze and understand the HPV-associated diseases. The concept was suggested by the characterization of distinct HPVs from different types of warts: HPV 2/27/57 from common warts, HPV 3/10/28 from flat warts, HPV 6/11 from condyloma acuminatum, and HPV 5/8 from lesions of epidermodysplasia verruciformis (EV). In this paper, I summarize recent advances in HPV study field, especially on HPV-associated cutaneous lesions. These include inclusion warts, HPV-associated epidermoid cysts, HPV type specific activation of melanogenesis, a double infection with HPV 1 and HPV 63 within a single cell, primary target cells and life cycle of the virus, and the identification of novel genes that are associated EV. The HPV-associated cutaneous lesions thus pose important problems to be resolved in virology and human pathology.